Background and Design. Intensive sequential chemotherapy with mitoxantrone 12 mg/m2/d on days 1 through 3; etoposide 200 mg/m2/d as a continuous infusion on days 8 through 10, cytarabine (Ara-C) 500 mg/m2/d as a continuous infusion on days 1 through 3 and 8 through 10 was administered to 13 patients aged less than 60 years (median 37, range 19-58) with previously treated acute nonlymphoblastic leukemia (ANLL). Results. Five patients had refractory ANLL (no response to prior therapy), one patient had early first relapse, four patients had late first relapse, three patients had second relapse. Forty-six percent (6 patients) of the patients achieved complete remission, fifteen percent did not respond to therapy and five died from therapy-related toxicity. Median duration of aplasia was 28 days. Non-hematological WHO grade 3 or more toxicity included infections (46%) in 6 patients, vomiting (30.7%), mucositis (53.8%), diarrhea (30.8%), skin rash (7.7%), clinical bleeding (30.8%), cardiac toxicity (7.7%), neurotoxicity (23.1%). Median disease-free survival was 215 days. One patient is alive at 825 days. Conclusion. These results, when combined with other studies concerning this chemotherapy protocol and keeping in mind the rate of increased toxicity, may indicate that it can be a good choice as a second line treatment protocol.